p190 Rho-GTPase activating protein associates with plexins and it is required for semaphorin signalling

Plexins are transmembrane receptors for semaphorins, guiding cell migration and axon extension. Plexin activation leads to the disassembly of integrin-based focal adhesive structures and to actin cytoskeleton remodelling and inhibition of cell migration; however, the underlying molecular mechanisms are unclear. We consistently observe a transient decrease of cellular RhoA-GTP levels upon plexin activation in adherent cells. One of the main effectors of RhoA downregulation is p190, a ubiquitously expressed GTPase activating protein (GAP). We show that, in p190-deficient fibroblasts, the typical functional activities mediated by plexins (such as cell collapse and inhibition of integrin-based adhesion) are blocked or greatly impaired. Notably, the functional response can be rescued in these cells by re-expressing exogenous p190, but not a mutant form specifically lacking RhoGAP activity. We furthermore demonstrate that semaphorin function is blocked in epithelial cells, primary endothelial cells and neuroblasts upon treatment with small interfering RNAs that knockdown p190 expression. Finally, we show that p190 transiently associates with plexins, and its RhoGAP activity is increased in response to semaphorin stimulation. We conclude that p190-RhoGAP is crucially involved in semaphorin signalling to the actin cytoskeleton, via interaction with plexins

Tankyrase inhibition impairs directional migration and invasion of lung cancer cells by affecting microtubule dynamics and polarity signals

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Human cardiac progenitor cell grafts as unrestricted source of supernumerary cardiac cells in healthy murine hearts

Human heart harbors a population of resident progenitor cells that can be isolated by stem cell antigen-1 antibody and expanded in culture. These cells can differentiate into cardiomyocytes in vitro and contribute to cardiac regeneration in vivo. However, when directly injected as single cell suspension, less than 1%-5% survive and differentiate. Among the major causes of this failure are the distressing protocols used to culture in vitro and implant progenitor cells into damaged hearts. Human cardiac progenitors obtained from the auricles of patients were cultured as scaffoldless engineered tissues fabricated using temperature-responsive surfaces. In the engineered tissue, progenitor cells established proper three-dimensional intercellular relationships and were embedded in self-produced extracellular matrix preserving their phenotype and multipotency in the absence of significant apoptosis. After engineered tissues were leant on visceral pericardium, a number of cells migrated into the murine myocardium and in the vascular walls, where they integrated in the respective textures. The study demonstrates the suitability of such an approach to deliver stem cells to the myocardium. Interestingly, the successful delivery of cells in murine healthy hearts suggests that myocardium displays a continued cell cupidity that is strictly regulated by the limited release of progenitor cells by the adopted source. When an unregulated cell source is added to the system, cells are delivered to the myocardium. The exploitation of this novel concept may pave the way to the setup of new protocols in cardiac cell therapy. STEM CELLS 2011;29:2051-206

Minimally invasive mitral valve surgery: State-of-the-art and our experience

The minimally invasive approach is becoming the standard-of-care for surgery of the mitral valve. As any less invasive strategy, it entails an increased surgical complexity. Standard-of-care mitral repair using the totally videoscopic approach is indeed reproducible; however, few specific data on patients with complex mitral valve disease are available in the published literature. The purpose of the present paper is to provide an overview of the current state-of-the-art in minimally invasive cardiac surgery, and a summary of recent evidence on the topic, with particular regard to the surgical techniques and comparisons with conventional surgery. The experience of the GVM Care and Research network in the field is also briefly reported

Climate Change and invasibility of the Antarctic benthos

Benthic communities living in shallow-shelf habitats in Antarctica (<100-m depth) are archaic in their structure and function. Modern predators, including fast-moving, durophagous (skeleton-crushing) bony fish, sharks, and crabs, are rare or absent; slow-moving invertebrates are the top predators; and epifaunal suspension feeders dominate many soft substratum communities. Cooling temperatures beginning in the late Eocene excluded durophagous predators, ultimately resulting in the endemic living fauna and its unique food-web structure. Although the Southern Ocean is oceanographically isolated, the barriers to biological invasion are primarily physiological rather than geographic. Cold temperatures impose limits to performance that exclude modern predators. Global warming is now removing those physiological barriers, and crabs are reinvading Antarctica. As sea temperatures continue to rise, the invasion of durophagous predators will modernize the shelf benthos and erode the indigenous character of marine life in Antarctica

Induction of resistance or enhancement to a transplantable murine plasmacytoma by transfer of non-immune leucocytes.

Newborn mice have a lower spontaneous resistance to the growth of a syngeneic plasmacytoma (MOPC-460) as compared to adult mice. The transfer of different leucocyte populations from non-immunized adult donors to newborn mice influence in a dual way the resistance to MOPC-460 growth, depending on the number of cells transferred. The transfer of a low number of neutrophils, thymus or spleen cells enhances the MOPC-460 takes. Higher numbers of neutrophils, thymus or bone marrow cells induce an effective protenction. By contrast, macrophages over a dose of 1 X 10(4) constantly produce a reduction of tumour growth